BACKGROUND. The management of foregut duplication cysts is controversial, especially in asymptomatic patients. The safety and accuracy of endoscopic ultrasound (EUS) and EUS-fine-needle aspiration EUS-FNA) in confirming the nature of cysts by using electron microscopy (EM) has not been reported. In this study, the authors describe the utility of demonstrating detached ciliary tufts (DCTs) in the diagnosis of foregut duplication cysts with EUS-FNA. METHODS. Consecutive patients with suspected mediastinal masses or mediastinal cysts on imaging studies were evaluated prospectively by EUS and EUS-FNA. Cyst fluid was examined by routine cytologic techniques. In two patients, EM was performed to confirm the nature of DCTs. RESULTS. Ten consecutive patients were evaluated with EUS and EUS-FNA. Seventy percent of the cysts were characterized by computed tomography (CT) scans as solid masses. The mean greatest cyst dimension measured 34 mm × 48 mm by EUS. Microscopic examination of the cyst content revealed mucinous material, cellular debris, and DCTs. The latter were seen in routine cytologic preparations and by EM. Patients were followed up to a median of 321 days. Due to EUS-FNA confirmatory diagnoses of foregut duplication cysts, none of the patients except 1 underwent surgical resection after developing pneumonia 6 months later. Histologic sections of the resected specimen confirmed the presence of (foregut cyst, bronchogenic type). All other patients were asymptomatic. Cysts size and nature did not change on repeated imaging studies. CONCLUSIONS. EUS was superior compared with CT scanning in characterizing foregut duplication cysts. EUS-FNA is safe and accurate in the diagnosis of foregut duplication cysts. The demonstration of DCTs in cyst fluid and the absence of malignant cells confirmed the benign nature of these lesions, allowing conservative and expectant management for these patients. © 2004 American Cancer Society.